Label: DEXMETHYLPHENIDATE HYDROCHLORIDE tablet

  • NDC Code(s): 43386-860-01, 43386-860-03, 43386-860-10, 43386-861-01, view more
    43386-861-03, 43386-861-10, 43386-862-01, 43386-862-03, 43386-862-10
  • Packager: Lupin Pharmaceuticals,Inc.
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: CII
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated November 20, 2020

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  • HIGHLIGHTS OF PRESCRIBING INFORMATION
    These highlights do not include all the information needed to use DEXMETHYLPHENIDATE HYDROCHLORIDE TABLETS safely and effectively. See full prescribing information for DEXMETHYLPHENIDATE HYDROCHLORIDE TABLETS.

    DEXMETHYLPHENIDATE HYDROCHLORIDE tablets, for oral use, CII Initial U.S. Approval: 2001

    WARNING: ABUSE AND DEPENDENCE

    See full prescribing information for complete boxed warning.

    • CNS stimulants, including Dexmethylphenidate Hydrochloride tablets, other methylphenidate- containing products, and amphetamines, have a high potential for abuse and dependence (5.1, 9.2, 9.3).
    • Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy (5.1, 9.2).while on therapy (5.1, 9.2).

    RECENT MAJOR CHANGES

    RECENT MAJOR CHANGES
    Boxed Warning1/2019
    Contraindications (4)1/2019
    Warnings and Precautions (5)1/2019

    INDICATIONS AND USAGE

    Dexmethylphenidate Hydrochloride is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) (1). (1)

    DOSAGE AND ADMINISTRATION

    • Administer orally twice daily, 4 hours apart with or without food(2)
    • For patients new to methylphenidate: Recommend starting dose of 5mg once daily (2.5 mg twice daily)(2.2).
    • For patients currently taking methylphenidate: Initiate Dexmethylphenidate Hydrochloride therapy with half (1/2) the current total daily dose of methylphenidate(2.3).
    • Titrate weekly in increments of 2.5 to 5 mg to a maximum of 20 mg/day (10 mg twice daily)(2.2).

    DOSAGE FORMS AND STRENGTHS

    Tablets: 2.5 mg, 5 mg, and 10 mg (3 (3)

    CONTRAINDICATIONS

    • Known hypersensitivity to methylphenidate or other components ofDexmethylphenidate Hydrochloride (4).
    • Concurrent treatment with a monoamine oxidase inhibitor (MAOI), or use of an MAOI within the preceding 14 days(4).

    WARNINGS AND PRECAUTIONS

    • Serious Cardiovascular Events: Sudden death has been reported in association with CNS-stimulant treatment at usual doses in pediatric patients with structural cardiac abnormalities or other serious heart problems. In adults, sudden death, stroke, and myocardial infarction have been reported. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, arrhythmias, or coronary artery disease (5.2).

    • Blood Pressure and Heart Rate Increases: Monitor blood pressure and pulse. Consider the benefits and risk in patients for whom an increase in blood pressure or heart rate would be problematic (5.3).
    • Psychotic Adverse Reactions: Use of stimulants may cause psychotic or manic symptoms in patients with no prior history, or exacerbation of symptoms in patients with pre-existing psychiatric illness. Evaluate for pre- existing psychotic or bipolar disorder prior to Dexmethylphenidate Hydrochloride tablets use (5.4).
    • Priapism: Cases of painful and prolonged penile erections and priapism have been reported with methylphenidate products. Immediate medical attention should be sought if signs or symptoms of prolonged penile erections or priapism are observed (5.5).
    • Peripheral Vasculopathy, Including Raynaud’s Phenomenon: Stimulants used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Careful observation for digital changes is necessary during treatment with ADHD stimulants (5.6).
    • Long-Term Suppression of Growth: Monitor height and weight at appropriate intervals in the pediatric population (5.7). (5)

    ADVERSE REACTIONS

    The most common adverse reactions (greater than or equal to 5% and twice the rate of placebo) in pediatric patients 6 to 17 years were abdominal pain, fever, nausea, and anorexia, ( 6.1) (6)

    To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 908-603-6000 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. (6)

    DRUG INTERACTIONS

    • Antihypertensive Drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed(7.1).
    • Halogenated Anesthetics: Avoid use of Dexmethylphenidate Hydrochloride tablets on the day of surgeryif halogenated anesthetics will be used(7.1).

    See 17 for Medication Guide.

    Revised: 5/2020

  • Table of Contents
  • BOXED WARNING (What is this?)

    Boxed Warning

    DRUG DEPENDENCE:

    Dexmethylphenidate hydrochloride tablets should be given cautiously to patients with a history of drug dependence or alcoholism. Chronic, abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful supervision is required during drug withdrawal from abusive use since severe depression may occur. Withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder that may require follow-up.

  • INDICATIONS AND USAGE

    Dexmethylphenidate Hydrochloride is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) [see Clinical Studies (14)].

  • DOSAGE AND ADMINISTRATION

    2.1 Pretreatment Screening

    Prior to treating pediatric patients and adults with central nervous system (CNS) stimulants, including Dexmethylphenidate Hydrochloride tablet, assess for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions 5.2].

    Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy. Maintain careful prescription records, educate patients about abuse, monitor for signs of abuse and overdose, and periodically reevaluate the need for Dexmethylphenidate Hydrochloride use [see Boxed Warning, Warnings and Precautions (5.1), Drug Abuse and Dependence (9)].

    2.2 Pediatric Patients with ADHD

    Patients New to Methylphenidate

    The recommended starting dose of Dexmethylphenidate Hydrochloride tablet for pediatric patients who are not currently taking racemic methylphenidate, or for patients who are on stimulants other than methylphenidate, is 5 mg daily (2.5 mg twice daily) with or without food.

    Patients Currently on Methylphenidate

    The recommended starting dose of Dexmethylphenidate Hydrochloride tablet for pediatric patients currently using methylphenidate is half the total daily dose of racemic methylphenidate.

    Titration Schedule

    The dose may be titrated weekly in increments of 2.5 to 5 mg to a maximum of 20 mg daily (10 mg twice daily). The dose should be individualized according to the needs and response of the patient.

    Maintenance/Extended Treatment

    Pharmacological treatment of ADHD may be needed for extended periods. Periodically reevaluate the long-term use of Dexmethylphenidate Hydrochloride and adjust dosage as needed.

    2.3 Administration Instructions

    Dexmethylphenidate Hydrochloride tablet is administered orally twice daily, at least 4 hours apart.

    2.4 Dose Reduction and Discontinuation

    If paradoxical aggravation of symptoms or other adverse reactions occur, reduce the dosage, or if necessary, discontinue Dexmethylphenidate Hydrochloride tablet. If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug should be discontinued.

  • DOSAGE FORMS & STRENGTHS

    Dexmethylphenidate Hydrochloride tablets are as follows:

    2.5 mg: blue, round, flat-faced, beveled-edge tablets, debossed with “862” on the one side and “n” on the other side

    5 mg: yellow, round, flat-faced, beveled-edge tablets, debossed with “860” on the one side and “n” on the other side

    10 mg: white, round, flat-faced, beveled-edge tablets, debossed with “861” on the one side and “n” on the other side

  • CONTRAINDICATIONS

    Hypersensitivity to methylphenidate or other components of Dexmethylphenidate Hydrochloride tablets. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with methylphenidate [see Adverse Reactions (6.1)].

    Concomitant treatment with monoamine oxidase inhibitors (MAOIs), or within 14 days following discontinuation of treatment with an MOAI, because of the risk of hypertensive crises [see Drug Interactions (7.1)].

  • WARNINGS AND PRECAUTIONS

    Potential for Abuse and Dependence

    CNS stimulants, including Dexmethylphenidate Hydrochloride, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [see Boxed Warning, Drug Abuse and Dependence (9.2, 9.3)].

    Serious Cardiovascular Reactions

    Sudden death, stroke and myocardial infarction have been reported in adults with CNS stimulant treatment at recommended doses. Sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious heart problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during Dexmethylphenidate Hydrochloride treatment.

    Blood Pressure and Heart Rate Increases

    CNS stimulants cause an increase in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 bpm). Individuals may have larger increases. Monitor all patients for hypertension and tachycardia.

    Psychiatric Adverse Reactions

    Exacerbation of Preexisting Psychosis

    CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder.

    Induction of a Manic Episode in Patients with Bipolar Disorder

    CNS stimulants may induce a manic or mixed mood episode in patients. Prior to initiating treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression).

    New Psychotic or Manic Symptoms

    CNS stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. If such symptoms occur, consider discontinuing Dexmethylphenidate Hydrochloride tablet. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared to 0 in placebo-treated patients.

    Priapism

    Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products in both pediatric and adult patients. Priapism was not reported with drug initiation but developed after some time on the drug, often subsequent to an increase in dose. Priapism has also appeared during a period of drug withdrawal (drug holidays or during discontinuation). Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.

    Peripheral Vasculopathy, Including Raynaud’s Phenomenon

    CNS stimulants, including Dexmethylphenidate Hydrochloride tablet, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

    Long-Term Suppression of Growth

    CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients.

    Careful follow-up of weight and height in patients ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated patients over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated pediatric patients (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development.

    Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including Dexmethylphenidate Hydrochloride tablet, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

  • ADVERSE REACTIONS

    The following are discussed in more detail in other sections of the labeling:

    • Abuse and Dependence [see Boxed Warning, Warnings and Precautions (5.1), Drug Abuse and Dependence (9.2, 9.3)]
    • Known hypersensitivity to methylphenidate or other ingredients of Dexmethylphenidate Hydrochloride tablet [see Contraindications (4)]
    • Hypertensive crisis with Concomitant Use of Monoamine Oxidase Inhibitors [see Contraindications (4), Drug Interactions (7.1)]
    • Serious Cardiovascular Reactions [see Warnings and Precautions (5.2)]
    • Blood Pressure and Heart Rate Increases [see Warnings and Precautions (5.3)]
    • Psychiatric Adverse Reactions [see Warnings and Precautions (5.4)]
    • Priapism [see Warnings and Precautions (5.5)]
    • Peripheral Vasculopathy, Including Raynaud’s phenomenon [see Warnings and Precautions (5.6)]
    • Long-term Suppression of Growth [see Warnings and Precautions (5.7)]

    1.1Clinical Trials Experience

    Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

    Clinical Trials Experience with Dexmethylphenidate Hydrochloride in Pediatric Patients with ADHD

    The safety data in this section is based on data related to Dexmethylphenidate Hydrochloride exposure during the premarketing development program in a total of 696 participants in clinical trials (684 patients, 12 healthy adult subjects). These participants received Dexmethylphenidate Hydrochloride 5, 10, or 20 mg/day. The 684 ADHD patients (ages 6 to 17 years) were evaluated in 2 controlled clinical studies, 2 clinical pharmacology studies, and 2 open-label long-term safety studies.

    Most Common Adverse Reactions (incidence of greater than or equal to 5% and at least twice placebo): abdominal pain, fever, anorexia, and nausea

    Adverse Reactions Leading to Discontinuation: Overall, 50 of 684 (7.3%) pediatric patients treated with Dexmethylphenidate Hydrochloride experienced an adverse reaction that resulted in discontinuation. The most common reasons for discontinuation were twitching (described as motor or vocal tics), anorexia, insomnia, and tachycardia (approximately 1% each).

    Table 1 enumerates adverse reactions for two, placebo-controlled, parallel group studies in pediatric patients with ADHD taking Dexmethylphenidate Hydrochloride tablet doses of 5, 10, and 20 mg/day. The table includes only those reactions that occurred in patients treated with Dexmethylphenidate Hydrochloride tablet for which the incidence was at least 5% and twice the incidence among placebo-treated patients.

    Table 1: Common Adverse Reactions in Pediatric Patients (6 to 17 years of age) with ADHD*

    System Organ ClassAdverse ReactionsDexmethylphenidate Hydrochloride tablet (N = 79)Placebo (N = 82)
    Body as a WholeAbdominal Pain15%6%
    Fever5%1%
    Digestive SystemAnorexia6%1%
    9%1%

    * ADHD: Attention Deficit Hyperactivity Disorder

    Postmarketing Experience

    The following additional adverse reactions have been identified during post approval use of dexmethylphenidate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

    Musculoskeletal: rhabdomyolysis

    Immune System Disorders: hypersensitivity reactions such as angioedema, anaphylactic reactions

    Adverse Reactions Reported with all Ritalin and Dexmethylphenidate Hydrochloride Formulations

    The following adverse reactions associated with the use of all Ritalin and Dexmethylphenidate Hydrochloride formulations were identified in clinical trials, spontaneous reports, and literature. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.

    Infections and Infestations: nasopharyngitis

    Blood and the Lymphatic System Disorders: leukopenia, thrombocytopenia, anemia

    Immune System Disorders: hypersensitivity reactions, including angioedema and anaphylaxis

    Metabolism and Nutrition Disorders: decreased appetite, reduced weight gain, and suppression of growth during prolonged use in pediatric patients

    Psychiatric Disorders: insomnia, anxiety, restlessness, agitation, psychosis (sometimes with visual and tactile hallucinations), depressed mood

    Nervous System Disorders: headache, dizziness, tremor, dyskinesia including choreoatheetoid movements, drowsiness, convulsions, cerebrovascular disorders (including vasculitis, cerebral hemorrhages and cerebrovascular accidents) , serotonin syndrome in combination with serotonergic drugs

    Eye Disorders: blurred vision, difficulties in visual accommodation

    Cardiac Disorders: tachycardia, palpitations, increased blood pressure, arrhythmias, angina pectoris

    Respiratory, Thoracic and Mediastinal Disorders: cough

    Gastrointestinal Disorders: dry mouth, nausea, vomiting, abdominal pain, dyspepsia

    Hepatobiliary Disorders: abnormal liver function, ranging from transaminase elevation to severe hepatic injury

    Skin and Subcutaneous Tissue Disorders: hyperhidrosis, pruritus, urticaria, exfoliative dermatitis, scalp hair loss, erythema multiforme rash, thrombocytopenic purpura

    Musculoskeletal and Connective Tissue Disorders: arthralgia, muscle cramps, rhabdomyolysis

    Investigations: weight loss (adult ADHD patients)

    Additional Adverse Reactions Reported with Other Methylphenidate-Containing Products

    The list below shows adverse reactions not listed with Ritalin and Dexmethylphenidate Hydrochloride formulations [see Adverse Reactions (6.2)] that have been reported with other methylphenidate products based on clinical trials data and post-marketing spontaneous reports.

    Blood and Lymphatic Disorders: pancytopenia

    Immune System Disorders: hypersensitivity reactions such as auricular swelling Psychiatric Disorders: affect lability, mania, disorientation, libido changes Nervous System Disorders: migraine

    Eye Disorders: diplopia, mydriasis

    Cardiac Disorders: sudden cardiac death, myocardial infarction, bradycardia, extrasystole, supraventricular tachycardia, ventricular extrasystole

    Vascular Disorders: peripheral coldness, Raynaud's phenomenon

    Respiratory, Thoracic and Mediastinal Disorders: pharyngolaryngeal pain, dyspnea

    Gastrointestinal Disorders: diarrhea, constipation

    Skin and Subcutaneous Tissue Disorders: angioneurotic edema, erythema, fixed drug eruption

    Musculoskeletal, Connective Tissue and Bone Disorders: myalgia, muscle twitching

    Renal and Urinary Disorders: hematuria

    Reproductive System and Breast Disorders: gynecomastia

    General disorders: fatigue

    Urogenital disorders: priapism

  • DESCRIPTION

    Dexmethylphenidate hydrochloride is the d-threo-enantiomer of racemic methylphenidate hydrochloride, which is a 50/50 mixture of the d-threo and l-threo-enantiomers. Dexmethylphenidate hydrochloride is a central nervous system (CNS) stimulant, available in three tablet strengths. Each tablet contains dexmethylphenidate hydrochloride 2.5, 5, or 10 mg for oral administration. Dexmethylphenidate hydrochloride is methyl α-phenyl-2-piperidineacetate hydrochloride, (R,R')-(+)-. Its empirical formula is C 14H 19NO 2•HCl. Its molecular weight is 269.77 and its structural formula is

    C:\Users\LdeepthI\Desktop\dexmethyl\dex-strctre.jpg

    Note: * = asymmetric carbon centers

    Dexmethylphenidate hydrochloride is a white crystalline powder. It is very slightly soluble in water and in alcohol. It dissolves in dilute solutions of mineral acids and in solutions of alkali hydroxides and carbonates

    Dexmethylphenidate hydrochloride tablets also contains the following inert ingredients: citric acid anhydrous, lactose monohydrate, magnesium stearate,  microcrystalline cellulose,  pregelatinized starch, sodium starch glycolate,  and FD&C Blue No.1  (2.5 mg tablets), D&C Yellow #10 (5 mg tablets); the 10 mg tablet contains no dye.

  • CLINICAL PHARMACOLOGY

    12.1 Mechanism ofAction

    Dexmethylphenidate hydrochloride is a central nervous system (CNS) stimulant. The mode of therapeutic action in ADHD is not known.

    12.2 Pharmacodynamics
    Pharmacodynamics

    Dexmethylphenidate is the more pharmacologically active d-enantiomer of racemic methylphenidate. Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

    Cardiac Electrophysiology

    A formal QT study has not been conducted in patients taking Dexmethylphenidate Hydrochloride tablet; however, a large QT effect is not expected. At the recommended maximum total daily dosage of 40 mg, Dexmethylphenidate Hydrochloride extended-release capsule does not prolong the QTc interval to any clinically relevant extent.

    12.3 Pharmacokinetics

    Absorption

    Dexmethylphenidate hydrochloride is readily absorbed following oral administration of Dexmethylphenidate Hydrochloride. In patients with ADHD, plasma dexmethylphenidate concentrations increase rapidly, reaching a maximum in the fasted state at about 1 to 1.5 hours postdose. No differences in the pharmacokinetics of Dexmethylphenidate Hydrochloride were noted following single and repeated twice daily dosing, thus indicating no significant drug accumulation in children with ADHD.

    After single dose administration of Dexmethylphenidate Hydrochloride tablet to pediatric patients, dexmethylphenidate exposure (Cmax and AUC0-inf ) showed dose-proportional increase in the range of 2.5 mg to 10 mg. Comparable plasma dexmethylphenidate levels were achieved following single dl-threo-methylphenidate HCl doses given as capsules in twice the total mg amount (equimolar with respect to Dexmethylphenidate Hydrochloride tablet).

    Approximately 90% of the dose is absorbed after oral administration of radiolabeled racemic methylphenidate. However, due to first pass metabolism the mean absolute bioavailability of dexmethylphenidate when administered in various formulations was 22% to 25%.

    Effect of Food

    High fat breakfast did not significantly affect Cmax or AUC0-inf of dexmethylphenidate when two 10 mg Dexmethylphenidate Hydrochloride tablets were administered, but delayed Tmax from 1.5 hours post dose to 2.9 hours post dose.

    Distribution

    The plasma protein binding of dexmethylphenidate is not known; racemic methylphenidate is bound to plasma proteins by 12% to 15%, independent of concentration. Dexmethylphenidate shows a volume of distribution of 2.65 ± 1.11 L/kg.

    Elimination

    Plasma dexmethylphenidate concentrations declined exponentially following oral administration of Dexmethylphenidate Hydrochloride tablets. Intravenous dexmethylphenidate was eliminated with a mean clearance of 0.40 ± 0.12 L/hr/kg. The mean terminal elimination half-life of dexmethylphenidate was approximately 2.2 hours.

    Metabolism

    In humans, dexmethylphenidate is metabolized primarily via de-esterification to d-α-phenyl-piperidine acetic acid (also known as d-ritalinic acid). This metabolite has little or no pharmacological activity. There is little or no in vivo interconversion to the l-threo-enantiomer.

    Excretion

    After oral dosing of radiolabeled racemic methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main urinary metabolite of racemic dl-methylphenidate was dl-ritalinic acid, accountable for approximately 80% of the dose. Urinary excretion of parent compound accounted for 0.5% of an intravenous dose.

    Studies in Special Populations

    Male and Female Patients

    Pharmacokinetic parameters were similar for boys and girls (mean age 10 years).

    In a single dose study conducted in adults, the mean dexmethylphenidate AUC0-inf values (adjusted for body weight) following single two 10 mg doses of Dexmethylphenidate Hydrochloride tablets were 25% to 35% higher in adult female volunteers (n = 6) compared to male volunteers (n = 9). Both Tmax and t1/2 were comparable for males and females.

    Racial or Ethnic Groups

    There is insufficient experience with the use of Dexmethylphenidate Hydrochloride tablets to detect ethnic variations in pharmacokinetics.

    Pediatric Patients

    The pharmacokinetics of dexmethylphenidate after Dexmethylphenidate Hydrochloride tablets administration have not been studied in children less than 6 years of age. When single doses of Dexmethylphenidate Hydrochloride tablet were given to children between the ages of 6 to 12 years and healthy adult volunteers, Cmax of dexmethylphenidate was similar, however, pediatric patients showed somewhat lower AUCs compared to the adults.

    Patients with Renal Impairment

    There is no experience with the use of Dexmethylphenidate Hydrochloride tablet in patients with renal impairment. Since renal clearance is not an important route of methylphenidate clearance, renal impairment is expected to have little effect on the pharmacokinetics of Dexmethylphenidate Hydrochloride tablet.

    Patients with Hepatic Impairment

    There is no experience with the use of Dexmethylphenidate Hydrochloride tablet in patients with hepatic impairment.

    Drug Interaction Studies

    Methylphenidate is not metabolized by cytochrome P450 (CYP) isoenzymes to a clinically relevant extent. Inducers or inhibitors of CYPs are not expected to have any relevant impact on methylphenidate pharmacokinetics. Conversely, the d- and l-enantiomers of methylphenidate did not relevantly inhibit CYP1A2, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A. Clinically, methylphenidate coadministration did not increase plasma concentrations of the CYP2D6 substrate desipramine.

    Pharmacodynamics

    Dexmethylphenidate hydrochloride is a central nervous system stimulant. Dexmethylphenidate hydrochloride, the more pharmacologically active enantiomer of the d- and l-enantiomers, is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. The mode of therapeutic action in Attention Deficit Hyperactivity Disorder (ADHD) is not known.

    Effects on QT Interval

    The effect of dexmethylphenidate hydrochloride extended-release capsules on the QT interval was evaluated in a double-blind, placebo- and open label active (moxifloxacin)-controlled study following single doses of dexmethylphenidate hydrochloride extended-release capsules, 40mg in 75 healthy volunteers. ECGs were collected up to  12 hours postdose. Frederica's method for heart rate correction was employed to derive the corrected QT interval (QTcF). The maximum mean prolongation of QTcF intervals was <5 ms, and the upper limit of the 90% confidence interval was below 10 ms for all time matched comparisons versus placebo. This was below the threshold of clinical concern and there was no evident-exposure response relationship.

    Pharmacokinetics

    Absorption

    Dexmethylphenidate hydrochloride is readily absorbed following oral administration of dexmethylphenidate hydrochloride tablets. In patients with ADHD, plasma dexmethylphenidate concentrations increase rapidly, reaching a maximum in the fasted state at about 1 to 1.5 hours postdose. No differences in the pharmacokinetics of dexmethylphenidate hydrochloride were noted following single and repeated twice daily dosing, thus indicating no significant drug accumulation in children with ADHD.

    When given to children as capsules in single doses of 2.5 mg, 5 mg, and 10 mg, C max and AUC 0-inf of dexmethylphenidate were proportional to dose. In the same study, plasma dexmethylphenidate levels were comparable to those achieved following single dl-threo-methylphenidate HCl doses given as capsules in twice the total mg amount (equimolar with respect to dexmethylphenidate hydrochloride).

    Food Effects

    In a single dose study conducted in adults, coadministration of 2 x 10 mg dexmethylphenidate hydrochloride with a high fat breakfast resulted in a dexmethylphenidate t max of 2.9 hours postdose as compared to 1.5 hours postdose when given in a fasting state. C max and AUC 0-inf were comparable in both the fasted and non-fasted states.

    Distribution

    Plasma dexmethylphenidate concentrations in children decline exponentially following oral administration of dexmethylphenidate hydrochloride.

    Metabolism and Excretion

    In humans, dexmethylphenidate is metabolized primarily to d-α-phenyl-piperidine acetic acid (also known as d-ritalinic acid) by de-esterification. This metabolite has little or no pharmacological activity. There is little or no in vivo interconversion to the l-threo-enantiomer, based on a finding of minute levels of l-threo-methylphenidate being detectable in a few samples in only 2 of 58 children and adults. After oral dosing of radiolabeled racemic methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main urinary metabolite was ritalinic acid, accountable for approximately 80% of the dose.

    In vitro studies showed that dexmethylphenidate did not inhibit cytochrome P450 isoenzymes.

    The mean plasma elimination half-life of dexmethylphenidate is approximately 2.2 hours.

    Special Populations

    Gender

    Pharmacokinetic parameters were similar for boys and girls (mean age 10 years).

    In a single dose study conducted in adults, the mean dexmethylphenidate AUC 0-inf values (adjusted for body weight) following single 2 x 10 mg doses of dexmethylphenidate hydrochloride were 25%-35% higher in adult female volunteers (n=6) compared to male volunteers (n=9). Both t max and t 1/2 were comparable for males and females.

    Race

    There is insufficient experience with the use of dexmethylphenidate hydrochloride to detect ethnic variations in pharmacokinetics.

    Age

    The pharmacokinetics of dexmethylphenidate after dexmethylphenidate hydrochloride administration have not been studied in children less than 6 years of age. When single doses of dexmethylphenidate hydrochloride were given to children between the ages of 6 to 12 years and healthy adult volunteers, C max of dexmethylphenidate was similar, however, children showed somewhat lower AUCs compared to the adults.

    Renal Insufficiency

    There is no experience with the use of dexmethylphenidate hydrochloride in patients with renal insufficiency. After oral administration of radiolabeled racemic methylphenidate in humans, methylphenidate was extensively metabolized and approximately 80% of the radioactivity was excreted in the urine in the form of ritalinic acid. Since very little unchanged drug is excreted in the urine, renal insufficiency is expected to have little effect on the pharmacokinetics of dexmethylphenidate hydrochloride.

    Hepatic Insufficiency

    There is no experience with the use of dexmethylphenidate hydrochloride in patients with hepatic insufficiency. (see PRECAUTIONS, Drug Interactions).

    Clinical Studies

    Dexmethylphenidate hydrochloride was evaluated in 2 double-blind, parallel-group, placebo-controlled trials in untreated or previously treated patients aged 6 to 17 years old with a DSM-IV diagnosis of Attention Deficit Hyperactivity Disorder (ADHD). Both studies included all three subtypes of ADHD, i.e., Combined Type, Predominantly Inattentive Type, or Predominantly Hyperactive-Impulsive Type. While both children and adolescents were included, the sample was predominantly children, thus, the findings are most pertinent to this age group. In both studies, the primary comparison of interest was dexmethylphenidate hydrochloride versus placebo.

    Dexmethylphenidate hydrochloride (5, 10, or 20 mg/day total dose), dl-threo-methylphenidate HCl (10, 20, or 40 mg/day total dose), and placebo were compared in a multicenter, 4-week, parallel group study in n=132 patients. Patients took the study medication twice daily, 3.5 to 5.5 hours between doses. Treatment was initiated with the lowest dose, and doses could be doubled at weekly intervals, depending on clinical response and tolerability, up to the maximum dose. The change from baseline to week 4 of the averaged score (an average of 2 ratings during the week) of the teacher's version of the SNAP-ADHD Rating Scale, a scale for assessing ADHD symptoms, was the primary outcome. Patients treated with dexmethylphenidate hydrochloride showed a statistically significant improvement in symptom scores from baseline over patients who received placebo.

    Figure 1 Mean Change from Baseline in Teacher SNAP-ADHD Scores in a 4-week Double-Blind Placebo-Controlled Study of Dexmethylphenidate Hydrochloride*

    C:\Users\LdeepthI\Desktop\dexmethyl\dex-fig1.jpg

    *Figure 1: Error bars represent the standard error of the mean.

    The other study, involving n=75 patients, was a multicenter, placebo-controlled, double-blind, 2-week treatment withdrawal study in children who were responders during a 6-week, open label initial treatment period. Children took study medication twice a day separated by a 3.5 to 5.5 hour interval. The primary outcome was proportion of treatment failures at the end of the 2-week withdrawal phase, where treatment failure was defined as a rating of 6 (much worse) or 7 (very much worse) on the Investigator Clinical Global Impression - Improvement (CGI-I). Patients continued on dexmethylphenidate hydrochloride showed a statistically significant lower rate of failure over patients who received placebo.

    Figure 2: Percent of Treatment Failures Following a 2 Week Double-Blind Placebo-Controlled Withdrawal of Dexmethylphenidate Hydrochloride

    C:\Users\LdeepthI\Desktop\dexmethyl\dex-fig2.jpg
  • PRECAUTIONS

    Hematologic Monitoring

    Periodic CBC, differential, and platelet counts are advised during prolonged therapy.

    Information for Patients

    Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with dexmethylphenidate and should counsel them in its appropriate use. A patient Medication Guide is available for dexmethylphenidate hydrochloride tablets. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.

    Priapism

    Advise patients, caregivers, and family members of the possibility of painful or prolonged penile erections (priapism). Instruct the patient to seek immediate medical attention in the event of priapism.

           Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud's phenomenon]

    • Instruct patients beginning treatment with dexmethylphenidate hydrochloride tablets about the risk of peripheral vasculopathy, including Raynaud's Phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red
    • Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes.
    • Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking dexmethylphenidate hydrochloride tablets
    • Further clinical evaluation (e.g. rheumatology referral) may be appropriate for certain patients.

    Drug Interactions

    Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. Because of possible effects on blood pressure, dexmethylphenidate hydrochloride should be used cautiously with pressor agents.

    Human pharmacologic studies have shown that racemic methylphenidate may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), and some antidepressants (tricyclics and selective serotonin reuptake inhibitors). Downward dose adjustments of these drugs may be required when given concomitantly with methylphenidate. It may be necessary to adjust the dosage and monitor plasma drug concentration (or, in the case of coumarin, coagulation times), when initiating or discontinuing concomitant methylphenidate.

    Carcinogenesis, Mutagenesis, and Impairment of Fertility

    Lifetime carcinogenicity studies have not been carried out with dexmethylphenidate. In a lifetime carcinogenicity study carried out in B6C3F1 mice, racemic methylphenidate caused an increase in hepatocellular adenomas, and in males only, an increase in hepatoblastomas at a daily dose of approximately 60 mg/kg/day. Hepatoblastoma is a relatively rare rodent malignant tumor type. There was no increase in total malignant hepatic tumors. The mouse strain used is sensitive to the development of hepatic tumors, and the significance of these results to humans is unknown.

    Racemic methylphenidate did not cause any increase in tumors in a lifetime carcinogenicity study carried out in F344 rats; the highest dose used was approximately 45 mg/kg/day.

    In a 24-week study of racemic methylphenidate in the transgenic mouse strain p53+/-, which is sensitive to genotoxic carcinogens, there was no evidence of carcinogenicity. Mice were fed diets containing the same concentrations as in the lifetime carcinogenicity study; the high-dose group was exposed to 60-74 mg/kg/day of racemic methylphenidate.

    Dexmethylphenidate was not mutagenic in the in vitro Ames reverse mutation assay, the in vitro mouse lymphoma cell forward mutation assay, or the in vivo mouse bone marrow micronucleus test.

    Racemic methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay or the in vitro mouse lymphoma cell forward mutation assay, and was negative in vivo in the mouse bone marrow micronucleus assay. However, sister chromatid exchanges and chromosome aberrations were increased, indicative of a weak clastogenic response, in an in vitro assay of racemic methylphenidate in cultured Chinese Hamster Ovary (CHO) cells.

    Racemic methylphenidate did not impair fertility in male or female mice that were fed diets containing the drug in an 18-week Continuous Breeding study. The study was conducted at doses of up to 160 mg/kg/day.

    Pregnancy

    Pregnancy Category C

    In studies conducted in rats and rabbits, dexmethylphenidate was administered orally at doses of up to 20 and 100 mg/kg/day, respectively, during the period of organogenesis. No evidence of teratogenic activity was found in either the rat or rabbit study; however, delayed fetal skeletal ossification was observed at the highest dose level in rats. When dexmethylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 20 mg/kg/day, postweaning body weight gain was decreased in male offspring at the highest dose, but no other effects on postnatal development were observed. At the highest doses tested, plasma levels (AUCs) of dexmethylphenidate in pregnant rats and rabbits were approximately 5 and 1 times, respectively, those in adults dosed with the maximum recommended human dose of 20 mg/day.

    Racemic methylphenidate has been shown to have teratogenic effects in rabbits when given in doses of 200 mg/kg/day throughout organogenesis.

    Adequate and well-controlled studies in pregnant women have not been conducted. Dexmethylphenidate hydrochloride tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

    Nursing Mothers

    It is not known whether dexmethylphenidate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if dexmethylphenidate hydrochloride is administered to a nursing woman.

    Pediatric Use

    The safety and efficacy of dexmethylphenidate hydrochloride in children under 6 years old have not been established. Long-term effects of dexmethylphenidate hydrochloride in children have not been well established (see WARNINGS).

    In a study conducted in young rats, racemic methylphenidate was administered orally at doses of up to 100 mg/kg/day for 9 weeks, starting early in the postnatal period (Postnatal Day 7) and continuing through sexual maturity (Postnatal Week 10). When these animals were tested as adults (Postnatal Weeks 13-14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day (approximately 6 times the maximum recommended human dose [MRHD] of racemic methylphenidate on a mg/m2 basis) or greater, and a deficit in the acquisition of a specific learning task was seen in females exposed to the highest dose (12 times the racemic MRHD on a mg/m2 basis). The no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (half the racemic MRHD on a mg/m2 basis). The clinical significance of the long-term behavioral effects observed in rats is unknown.

  • DRUG INTERACTIONS

    7.1 Clinically Important Interactions withDexmethylphenidate Hydrochloride

    Table 2 presents clinically important drug interactions with Dexmethylphenidate Hydrochloride.

    Table 2: Clinically Important Drug Interactions with Dexmethylphenidate Hydrochloride

    Monoamine Oxidase Inhibitors (MAOI)
    Clinical ImpactConcomitant use of MAOIs and CNS stimulants, including Dexmethylphenidate Hydrochloride, can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure [see Contraindications (4)].
    InterventionConcomitant use of Dexmethylphenidate Hydrochloride with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated.
    Examples

    selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue

    Antihypertensive Drugs
    Clinical ImpactDexmethylphenidate Hydrochloride may decrease the effectiveness of drugs used to treat hypertension [see Warnings and Precautions (5.3)].
    InterventionAdjust the dosage of the antihypertensive drug as needed.
    ExamplesPotassium-sparing and thiazide diuretics, calcium channel blockers, angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta blockers, centrally acting alpha-2 receptor agonists
    Halogenated Anesthetics
    Clinical ImpactConcomitant use of halogenated anesthetics and Dexmethylphenidate Hydrochloride may increase the risk of sudden blood pressure and heart rate increase during surgery.
    InterventionMonitor blood pressure and avoid use of Dexmethylphenidate Hydrochloride in patients being treated with anesthetics on the day of surgery.
    Exampleshalothane, isoflurane, enflurane, desflurane, sevoflurane

  • USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    Pregnancy Exposure Registry

    There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including Dexmethylphenidate Hydrochloride tablets, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy registry for ADHD medications at 1-866-961-2388 or visit https://womensmentalhealth.org/adhd- medications/.

    Risk Summary

    Dexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. Published studies and postmarketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There may be risks to the fetus associated with the use of CNS stimulants use during pregnancy (see Clinical Considerations). Embryo-fetal development studies in rats showed delayed fetal skeletal ossification at doses up to 5 times the maximum recommended human dose (MRHD) of 20 mg/day given to adults based on plasma levels. A decrease in pup weight in males was observed in a pre- and post-natal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 5 times the MRHD of 20 mg/day given to adults based on plasma levels. Plasma levels in adults were comparatively similar to plasma levels in adolescents (see Data).

    The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

    Clinical Considerations

    Fetal/Neonatal Adverse Reactions

    CNS stimulants such as Dexmethylphenidate Hydrochloride, can cause vasoconstriction and thereby decrease placental perfusion. No fetal and/or neonatal adverse reactions have been reported with the use of therapeutic doses of methylphenidate during pregnancy; however, premature delivery and low birth weight infants have been reported in amphetamine-dependent mothers.

    Data

    Animal Data

    In embryo-fetal development studies conducted in rats and rabbits, dexmethylphenidate was administered orally at doses of up to 20 and 100 mg/kg/day, respectively, during the period of organogenesis. No evidence of malformations was found in either the rat or rabbit study; however, delayed fetal skeletal ossification was observed at the highest dose level in rats. When dexmethylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 20 mg/kg/day, post-weaning body weight gain was decreased in male offspring at the highest dose, but no other effects on postnatal development were observed. At the highest doses tested, plasma levels (AUCs) of dexmethylphenidate in pregnant rats and rabbits were approximately 5 and 1 times, respectively, those in adults dosed with the MRHD of 20 mg/day.

    Racemic methylphenidate has been shown to cause malformations (increased incidence of fetal spina bifida) in rabbits when given in doses of 200 mg/kg/day throughout organogenesis.

    8.2 Lactation

    Risk Summary

    Dexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. Limited published literature, based on milk sampling from seven mothers reports that methylphenidate is present in human milk, which resulted in infant doses of 0.16% to 0.7% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.1 and 2.7. There are no reports of adverse effects on the breastfed infant and no effects on milk production. Long-term neurodevelopmental effects on infants from stimulant exposure are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Dexmethylphenidate Hydrochloride and any potential adverse effects on the breastfed infant from Dexmethylphenidate Hydrochloride or from the underlying maternal condition.

    Clinical Considerations

    Monitor breastfeeding infants for adverse reactions, such as agitation, insomnia, anorexia, and reduced weight gain.

    8.4 Pediatric Use

    The safety and effectiveness of Dexmethylphenidate Hydrochloride have been established in pediatric patients ages 6 to 17 years in two adequate and well-controlled clinical trials [see Clinical Studies (14)].

    The safety and effectiveness of Dexmethylphenidate Hydrochloride in pediatric patients less than 6 years have not been established. The long-term efficacy of Dexmethylphenidate Hydrochloride in pediatric patients has not been established.

    Long Term Suppression of Growth

    Growth should be monitored during treatment with stimulants, including Dexmethylphenidate Hydrochloride tablets. Pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see Warnings and Precautions (5.7)].

    Juvenile Animal Toxicity Data

    Rats treated with racemic methylphenidate early in the postnatal period through sexual maturation demonstrated a decrease in spontaneous locomotor activity in adulthood. A deficit in acquisition of a specific learning task was observed in females only. The doses at which these findings were observed are at least 6 times the MRHD of 60 mg/day given to children on a mg/m2 basis.

    In a study conducted in young rats, racemic methylphenidate was administered orally at doses of up to 100 mg/kg/day for 9 weeks, starting early in the postnatal period (postnatal Day 7) and continuing through sexual maturity (postnatal week 10). When these animals were tested as adults (postnatal Weeks 13 to 14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day (approximately 4 times the MRHD of 60 mg of racemic methylphenidate given to children on a mg/m2 basis) or greater, and a deficit in the acquisition of a specific learning task was seen in females exposed to the highest dose (8 times the MRHD given to children on a mg/m2 basis).

    The no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (approximately 0.5 times the MRHD given to children on a mg/m2 basis). The clinical significance of the long-term behavioral effects observed in rats is unknown.

    8.5 Geriatric Use

    Dexmethylphenidate Hydrochloride has not been studied in the geriatric population.

  • DRUG ABUSE AND DEPENDENCE

    9.1 ControlledSubstance

    Dexmethylphenidate Hydrochloride tablet contains dexmethylphenidate hydrochloride, a Schedule II controlled substance.

    9.2 Abuse

    CNS stimulants, including Dexmethylphenidate Hydrochloride tablet, other methylphenidate-containing products, and amphetamines have a high potential for abuse. Abuse is characterized by impaired control over drug use despite harm, and craving.

    Signs and symptoms of CNS stimulant abuse include increased heart rate, respiratory rate, blood pressure, and/or sweating, dilated pupils, hyperactivity, restlessness, insomnia, decreased appetite, loss of coordination, tremors, flushed skin, vomiting, and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed. Abusers of CNS stimulants may chew, snort, inject, or use other unapproved routes of administration which may result in overdose and death [see Overdosage (10)].

    To reduce the abuse of CNS stimulants including Dexmethylphenidate Hydrochloride tablet, assess the risk of abuse prior to prescribing. After prescribing, keep careful prescription records, educate patients and their families about abuse and on proper storage and disposal of CNS stimulants [see How Supplied/Storage and Handling (16)], monitor for signs of abuse while on therapy, and reevaluate the need for Dexmethylphenidate Hydrochloride tablet use.

    9.3 Dependence

    Tolerance

    Tolerance (a state of adaptation in which exposure to a drug results in a reduction of the drug’s desired and/or undesired effects over time) can occur during chronic therapy with CNS stimulants, including Dexmethylphenidate Hydrochloride tablet.

    Dependence

    Physical dependence (which is manifested by a withdrawal syndrome produced by abrupt cessation, rapid dose reduction, or administration of an antagonist) can occur in patients treated with CNS stimulants including Dexmethylphenidate Hydrochloride tablet. Withdrawal symptoms after abrupt cessation following prolonged high-dosage administration of CNS stimulants include dysphoric mood; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.

  • NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

    Carcinogenesis

    Lifetime carcinogenicity studies have not been carried out with dexmethylphenidate. In a lifetime carcinogenicity study carried out in B6C3F1 mice, racemic methylphenidate caused an increase in hepatocellular adenomas, and in males only, an increase in hepatoblastomas was seen at a daily dose of approximately 60 mg/kg/day. This dose is approximately 2 times the MRHD of 60 mg/day of racemic methylphenidate given to children on a mg/m2 basis. Hepatoblastoma is a relatively rare rodent malignant tumor type. There was no increase in total malignant hepatic tumors. The mouse strain used is sensitive to the development of hepatic tumors and the significance of these results to humans is unknown.

    Racemic methylphenidate did not cause any increase in tumors in a lifetime carcinogenicity study carried out in F344 rats; the highest dose used was approximately 45 mg/kg/day, which is approximately 4 times the MRHD (children) of 60 mg/day of racemic methylphenidate on a mg/m2 basis.

    In a 24-week carcinogenicity study with racemic methylphenidate in the transgenic mouse strain p53+/-, which is sensitive to genotoxic carcinogens, there was no evidence of carcinogenicity. Male and female mice were fed diets containing the same concentrations as in the lifetime carcinogenicity study; the high-dose group was exposed to 60-74 mg/kg/day of racemic methylphenidate.

    Mutagenesis

    Dexmethylphenidate was not mutagenic in the in vitro Ames reverse mutation assay, in the in vitro mouse lymphoma cell forward mutation assay, or in the in vivo mouse bone marrow micronucleus test. In an in vitro assay using cultured Chinese Hamster Ovary (CHO) cells treated with racemic methylphenidate, sister chromatid exchanges and chromosome aberrations were increased, indicative of a weak clastogenic response.

    Impairment of Fertility

    No human data on the effect of methylphenidate on fertility are available.

    Fertility studies have not been conducted with dexmethylphenidate. Racemic methylphenidate did not impair fertility in male or female mice that were fed diets containing the drug in an 18-week continuous breeding study. The study was conducted at doses of up to 160 mg/kg/day, approximately 10 times the maximum recommended human dose of 60 mg/day of racemic methylphenidate given adolescents on a mg/m2 basis.

  • CLINICAL STUDIES

    The efficacy of Dexmethylphenidate Hydrochloride tablet for the treatment of ADHD was established in two double-blind, parallel-group, placebo- controlled trials in untreated or previously treated patients (ages 6 to 17 years old) who met DSM-IV criteria for ADHD inattentive, hyperactive-impulsive, or combined inattentive/hyperactive-impulsive subtypes. The sample was predominantly younger (ages 6 to 12 years); thus, the findings are most pertinent to this age group. In Study 1, patients were randomized to receive either Dexmethylphenidate Hydrochloride tablet (5, 10, or 20 mg/day total dose), racemic methylphenidate HCl (10, 20, or 40 mg/day total dose), or placebo in a multicenter, 4-week, parallel group study in 132 pediatric patients. Patients received study medication twice daily separated by a 3.5 to 5.5 hours interval. Treatment was initiated with the lowest dose, and doses could be doubled at weekly intervals, depending on clinical response and tolerability, up to the maximum dose. The primary outcome was change from baseline to week 4 of the average score (an average of 2 ratings during the week) of the teacher’s version of the SNAP-ADHD Rating Scale. This 18 item scale measures ADHD symptoms of inattention and hyperactivity/impulsivity, rated on a scale of 0 (Not at All) to 3 (Very Much). Patients treated with Dexmethylphenidate Hydrochloride tablet showed a statistically significant improvement in symptom scores from baseline over patients who received placebo (Table 3).

    Table 3: Summary of Efficacy Results from ADHD Acute-Phase Study in Pediatric Patients (6 – 17 years) (Study 1)

    Study NumberTreat Group

    Primary Efficacy Measure:

    Teacher SNAP-ADHD Total Score

    Mean Baseline Score (SD)Mean Change from Baseline Week 4 Score (SD)
    Study 1

    Dexmethylphenidate Hydrochloride tablets 5-20 mg/dayb

    (n = 44)

    Placebo (n = 42)

    1.4 (0.7) (n = 42)

    1.6 (0.7) (n = 41)

    - 0.7 (0.7) (n = 42)

    - 0.2 (0.7) (n = 39)

    ADHD: Attention Deficit Hyperactivity Disorder; SD: standard deviation; n = number of patients available at the assessment

    time point.

    aAverage of two ratings.

    bStatistically significantly different from placebo

    Study 2 was a multicenter, placebo-controlled, double-blind, 2-week treatment withdrawal study in 75 children (ages 6 to 12 years) who were responders during a 6-week, open-label initial treatment period. Children took study medication twice a day separated by a 3.5 to 5.5 hour interval. The primary outcome was proportion of treatment failures at the end of the

    2-week withdrawal phase, where treatment failure was defined as a rating of 6 (much worse) or 7 (very much worse) on the Investigator Clinical Global Impression - Improvement (CGI-I). Patients continued on Dexmethylphenidate Hydrochloride tablet showed a statistically significant lower rate of failure over patients who received placebo (Table 4).

    Table 4: Summary of Efficacy Results From ADHD Randomized Withdrawal Study in Pediatric Patients (6 – 17 years) (Study 2)

    Study NumberTreatment GroupPrimary Efficacy Measure: Proportion of Treatment failure a
    Number of Treatment Failure/ Number of Randomized PatientsPercentage
    Study 2

    Dexmethylphenidate Hydrochloride tablet 5-20 mg/day b

    Placebo

    6/35

    25/40

    17.1%

    62.5%

    ADHD: Attention Deficit Hyperactivity Disorder.
    aOne patient did not have the value at Visit 10 and hence not included in this analysis.

    bStatistically significantly different from placebo.

  • HOW SUPPLIED

    2.5 mg Tablets: blue, round, flat-faced, beveled-edge tablets, debossed with “862” on the one side and “n” on the other side.

    Bottles of 30…………………………………………………. NDC 43386-862-03

    Bottles of 100............................................................................NDC 43386-862-01

    Bottles of 1000….……………………………………………..NDC 43386-862-10

    5 mg Tablets: yellow, round, flat-faced, beveled-edge tablets, debossed with “860” on the one side and “n” on the other side.

    Bottles of 30……………………………………………….... NDC 43386-860-03

    Bottles of 100........................................................................... NDC 43386-860-01

    Bottles of 1000…………………………………………….... NDC 43386-860-10

    10 mg Tablets: white, round, flat-faced, beveled-edge tablets, debossed with “861” on the one side and “n” on the other side.

    Bottles of 30…………………………………………………. NDC 43386-861-03

    Bottles of 100........................................................................... NDC 43386-861-01

    Bottles of 1000………………………………………………. NDC 43386-861-10

    Store at 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C and 30°C (59°F to 86°F) [See USP Controlled Room Temperature].

    Protect from light and moisture.

    Dispense in tight, light-resistant container (USP), with a child-resistant closure.

    Disposal

    Comply with local laws and regulations on drug disposal of CNS stimulants. Dispose of remaining, unused, or expired Dexmethylphenidate Hydrochloride tablet by a medicine takeback program or by an authorized collector registered with the Drug Enforcement Administration. If no take-back program or authorized collector is available, mix Dexmethylphenidate Hydrochloride tablet with an undesirable, nontoxic substance to make it less appealing to children and pets. Place the mixture in a container such as a sealed plastic bag and discard Dexmethylphenidate Hydrochloride tablet in the household trash.

  • 88436-1 - Section Title Not Found In Database

    Advise the patient to read the FDA-approved patient labeling (Medication Guide).

    Controlled Substance Status/High Potential for Abuse and Dependence

    Advise patients that Dexmethylphenidate Hydrochloride tablet is a controlled substance, and it can be abused and lead to dependence. Instruct patients that they should not give Dexmethylphenidate Hydrochloride tablet to anyone else. Advise patients to store Dexmethylphenidate Hydrochloride tablet in a safe place, preferably locked, to prevent abuse. Advise patients to comply with laws and regulations on drug disposal. Advise patients to dispose of remaining, unused, or expired Dexmethylphenidate Hydrochloride tablet by a medicine take-back program if available [see Boxed Warning, Warnings and Precautions (5.1), Drug Abuse and Dependence (9.1, 9.2, 9.3), How Supplied/Storage and Handling (16)].

    Serious Cardiovascular Risks

    Advise patients that there is a potential serious cardiovascular risk including sudden death, myocardial infarction, stroke, and hypertension with Dexmethylphenidate Hydrochloride tablet use. Instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease [see Warnings and Precautions (5.2)].

    Blood Pressure and Heart Rate Increases

    Instruct patients that Dexmethylphenidate Hydrochloride tablet can cause elevations of their blood pressure and pulse rate [see Warnings and Precautions (5.3)].

    Psychiatric Risks

    Advise patients that Dexmethylphenidate Hydrochloride tablet, at recommended doses, can cause psychotic or manic symptoms, even in patients without prior history of psychotic symptoms or mania [see Warnings and Precautions (5.4)].

    Priapism

    Advise patients of the possibility of painful or prolonged penile erections (priapism). Instruct them to seek immediate medical attention in the event of priapism [see Warnings and Precautions (5.5)].

    Circulation Problems in Fingers and Toes [Peripheral Vasculopathy, Including Raynaud’s Phenomenon]

    Instruct patients beginning treatment with Dexmethylphenidate Hydrochloride tablet about the risk of peripheral vasculopathy, including Raynaud’s phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red. Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes.

    Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking Dexmethylphenidate Hydrochloride tablet. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients [see Warnings and Precautions (5.6)].

    Suppression of Growth

    Advise patients that Dexmethylphenidate Hydrochloride tablet may cause slowing of growth and weight loss [see Warnings and Precautions (5.7)].

    Pregnancy Registry

    Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in patients exposed to

    ADHD medications, including DEXMETHYLPHENIDATE HYDROCHLORIDE TABLET, during pregnancy [see Use in Specific Populations (8.1)].

    Manufactured for:

    Lupin Pharmaceuticals, Inc.

    Baltimore, MD 21202

    Manufactured by:

    Novel Laboratories, Inc.

    Somerset, NJ 08873

    SAP code: 264872

    Rev. 03/2020

  • SPL MEDGUIDE

    MEDICATION GUIDE

    Dexmethylphenidate (dex meth ill fen i date) Hydrochloride Tablets CII

    What is the most important information I should know about Dexmethylphenidate Hydrochloride tablet?

    Dexmethylphenidate Hydrochloride tablet is a federal controlled substance (CII) because it can be abused or lead to dependence. Keep Dexmethylphenidate Hydrochloride tablet in a safe place to prevent misuse and abuse. Selling or giving away Dexmethylphenidate Hydrochloride tablet may harm others, and is against the law.

    Tell your doctor if you or your child have abused or been dependent on alcohol, prescription medicines, or street drugs.

    The following have been reported with use of methylphenidate hydrochloride and other stimulant medicines:

    1. Heart-related problems:

    • sudden death in patients who have heart problems or heart defects
    • stroke and heart attack in adults
    • increased blood pressure and heart rate

    Tell your doctor if you or your child have any heart problems, heart defects, high blood pressure, or a family history of these problems.

    Your doctor should check you or your child carefully for heart problems before starting Dexmethylphenidate Hydrochloride tablet.

    Your doctor should check you or your child’s blood pressure and heart rate regularly during treatment with Dexmethylphenidate Hydrochloride tablet.

    Call your doctor right away if you or your child has any signs of heart problems such as chest pain, shortness of breath, or fainting while taking Dexmethylphenidate Hydrochloride tablet.

    2. Mental (Psychiatric) problems: All Patients

    new or worse behavior and thought problems
    new or worse bipolar illness
    new or worse aggressive behavior or hostility
    new psychotic symptoms (such as hearing voices, believing things that are not true, are suspicious) or new manic symptoms


    Tell your doctor about any mental problems you or your child have, or about a family history of suicide, bipolar illness, or depression.

    Call your doctor right away if you or your child have any new or worsening mental symptoms or problems while taking Dexmethylphenidate Hydrochloride tablet, especially seeing or hearing things that are not real, believing things that are not real, or are suspicious.

    What is Dexmethylphenidate Hydrochloride tablet?

    • Dexmethylphenidate Hydrochloride tablet is a central nervous system stimulant (CNS) prescription medicine. It is used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). Dexmethylphenidate Hydrochloride tablet may help increase attention and decrease impulsivenessandhyperactivityinpatientswithADHD.
    • Dexmethylphenidate Hydrochloride tablet should be used as a part of a total treatment program for ADHD that may include counseling or other therapies.

    Who should not take Dexmethylphenidate Hydrochloride tablet:

    Dexmethylphenidate Hydrochloride tablet should not be taken if you or your child:

    • are allergic to methylphenidate hydrochloride, or any of the ingredients in Dexmethylphenidate Hydrochloride tablet. See the end of this Medication Guide for a complete list of ingredients inDexmethylphenidate Hydrochloride tablet.
    • are taking or have taken within the past 14 days an anti-depression medicine called a monoamine oxidase

    Dexmethylphenidate Hydrochloride tablet may not be right for you or your child. Before starting Dexmethylphenidate Hydrochloride tablet, tell your or your child’s doctor about all health conditions (or a family history of) including:

    • heart problems, heart defects, high bloodpressure
    • mental problems including psychosis, mania, bipolar illness, or depression
    • circulation problems in fingers ortoes
    • if you are pregnant or plan to become pregnant. It is not known if Dexmethylphenidate Hydrochloride tablet will harm your unborn baby.
    • There is a pregnancy registry for females who are exposed to ADHD medications, including Dexmethylphenidate Hydrochloride tablet during pregnancy. The purpose of the registry is to collect information about the health of females exposed to Dexmethylphenidate Hydrochloride tablet and their baby. If you or your child becomes pregnant during treatment with Dexmethylphenidate Hydrochloride tablet, talk to your healthcare provider about registering with the National Pregnancy Registry of ADHD medications at 1-866-961-2388 or visit online at https://womensmentalhealth.org/adhd-medications/.
    • if you are breastfeeding or plan to breastfeed. Dexmethylphenidate Hydrochloride tablet passes into your breast milk. Talk to your healthcare provider about the best way to feed the baby during treatment with Dexmethylphenidate Hydrochloride tablet.

    Tell your doctor about all of the medicines that you or your child takes including prescription and over-the- counter medicines, vitamins, and herbal supplements. Dexmethylphenidate Hydrochloride tablet and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be adjusted while taking Dexmethylphenidate Hydrochloride tablet.

    Your doctor will decide whether Dexmethylphenidate Hydrochloride tablet can be taken with other medicines.

    Especially tell your doctor if you or your child takes:

    • anti-depression medicines includingMAOIs
    • blood pressure medicines(anti-hypertensive)

    Know the medicines that you or your child takes. Keep a list of your medicines with you to show your doctor and pharmacist.

    • You should not take Dexmethylphenidate Hydrochloride tablet on the day of your operation if a certain type of anesthetic is used. This is because there is a chance of a sudden rise in blood pressure and heart rate during the operation.

    Do not start any new medicine while taking Dexmethylphenidate Hydrochloride tablet without talking to your doctor first.

    How should Dexmethylphenidate Hydrochloride tablet be taken?

    • Take Dexmethylphenidate Hydrochloride tablet exactly as prescribed. Your doctor may adjust the dose until it is right for you or your child.
    • Take Dexmethylphenidate Hydrochloride tablet twice daily, at least 4 hours apart.
    • Dexmethylphenidate Hydrochloride tablet may be taken with or without food.
    • From time to time, your doctor may stop Dexmethylphenidate Hydrochloride tablet treatment for a while to check ADHD symptoms.
    • Your doctor may do regular checks of the blood, heart, and blood pressure while taking Dexmethylphenidate Hydrochloride tablet.
    • Children should have their height and weight checked often while taking Dexmethylphenidate Hydrochloride tablet. Dexmethylphenidate Hydrochloride tablet treatment may be stopped if a problem is found during these check-ups.
    • In case of poisoning call your poison control center at 1-800-222-1222 right away, or go to the nearest hospital emergency room.

    What are the possible side effects of Dexmethylphenidate Hydrochloride tablet?
    Dexmethylphenidate Hydrochloride tablet may cause serious side effects, including:

    • See “What is the most important information I should know about Dexmethylphenidate Hydrochloride tablet?” for information on reported heart and mental problems.
    • painful and prolonged erections (priapism) have occurred with methylphenidate. If you or your child develops priapism, seek medical help right away. Because of the potential for lasting damage, priapism should be evaluated by a doctor immediately.
    • circulation problems in fingers and toes (Peripheral Vasculopathy, including Raynaud’s phenomenon):
    • fingers or toes may feel numb, cool, painful
    • fingers or toes may change color from pale, to blue, to red

    Tell your doctor if you or your child have, numbness, pain, skin color change, or sensitivity to temperature in the fingers or toes.

    • Call your doctor right away if you have or your child has any signs of unexplained wounds appearing on fingers or toes while taking Dexmethylphenidate Hydrochloride tablet.
    • slowing of growth (height and weight) in children Common side effects include:
    • abdominal pain
    • fever
    • anorexia
    • nausea

    Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

    How should I store Dexmethylphenidate Hydrochloride tablet?

    • Store Dexmethylphenidate Hydrochloride tablet in a safe place and in a tightly closed container at room temperature between 68°F to 77°F (20°C to 25°C).
    • Protect from light.
    • Dispose of remaining, unused, or expired Dexmethylphenidate Hydrochloride tablet by a medicine take-back program at authorized collection sites such as retail pharmacies, hospital or clinic pharmacies, and law enforcement locations. If no take-back program or authorized collector is available, mix Dexmethylphenidate Hydrochloride tablet with an undesirable, nontoxic substance such as dirt, cat litter, or used coffee grounds to make it less appealing to children and pets. Place the mixture in a container such as a sealed plastic bag and throw away (discard) Dexmethylphenidate Hydrochloride tablet in the household trash.

    • Keep Dexmethylphenidate Hydrochloride tablet and all medicines out of the reach of children.

    General information about the safe and effective use of Dexmethylphenidate Hydrochloride tablet.

    Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your pharmacist or doctor for information about Dexmethylphenidate Hydrochloride tablet that is written for healthcare professionals. Do not use Dexmethylphenidate Hydrochloride tablet for a condition for which it was not prescribed. Do not give Dexmethylphenidate Hydrochloride tablet to other people, even if they have the same symptoms that you have. It may harm them and it is against the law.

    What are the ingredients in Dexmethylphenidate Hydrochloride tablet?

    Active ingredient: dexmethylphenidate hydrochloride

    Inactive ingredients: citric acid anhydrous, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch, sodium starch glycolate, and FD&C Blue No.1 (2.5 mg tablets), D&C Yellow #10 (5 mg tablets); the 10 mg tablet contains no dye.

    Manufactured for:

    Lupin Pharmaceuticals, Inc.

    Baltimore, MD 21202

    Manufactured by:

    Novel Laboratories, Inc.

    Somerset, NJ 08873

    SAP code: 264872

    Rev: 03/2020

  • PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

    2.5 mg Tablets

    30 count

    2.5 mg-30

    2.5 mg Tablets

    100 count

    2.5 mg - 100

    2.5 mg Tablets

    1000 count

    2.5 mg - 1000 c ount

    5 mg Tablets

    30 count

    5 mg - 30 count

    5 mg Tablets

    100 count

    5 mg - 100

    5 mg Tablets

    1000 count

    5 mg - 1000

    10 mg Tablets

    30 Count

    10 mg - 30 count

    10 mg Tablets

    100 Count.

    10 mg - 100

    10 mg Tablets

    1000 Count

    10 mg - 1000
  • INGREDIENTS AND APPEARANCE
    DEXMETHYLPHENIDATE HYDROCHLORIDE 
    dexmethylphenidate hydrochloride tablet
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:43386-862
    Route of AdministrationORALDEA ScheduleCII    
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    DEXMETHYLPHENIDATE HYDROCHLORIDE (UNII: 1678OK0E08) (DEXMETHYLPHENIDATE - UNII:M32RH9MFGP) DEXMETHYLPHENIDATE HYDROCHLORIDE2.5 mg
    Inactive Ingredients
    Ingredient NameStrength
    ANHYDROUS CITRIC ACID (UNII: XF417D3PSL)  
    LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
    STARCH, CORN (UNII: O8232NY3SJ)  
    SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
    FD&C BLUE NO. 1 (UNII: H3R47K3TBD)  
    Product Characteristics
    ColorblueScoreno score
    ShapeROUNDSize7mm
    FlavorImprint Code 862;n
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:43386-862-101000 in 1 BOTTLE; Type 0: Not a Combination Product12/04/2015
    2NDC:43386-862-01100 in 1 BOTTLE; Type 0: Not a Combination Product12/04/2015
    3NDC:43386-862-0330 in 1 BOTTLE; Type 0: Not a Combination Product12/04/2015
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA20453412/04/2015
    DEXMETHYLPHENIDATE HYDROCHLORIDE 
    dexmethylphenidate hydrochloride tablet
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:43386-860
    Route of AdministrationORALDEA ScheduleCII    
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    DEXMETHYLPHENIDATE HYDROCHLORIDE (UNII: 1678OK0E08) (DEXMETHYLPHENIDATE - UNII:M32RH9MFGP) DEXMETHYLPHENIDATE HYDROCHLORIDE5 mg
    Inactive Ingredients
    Ingredient NameStrength
    ANHYDROUS CITRIC ACID (UNII: XF417D3PSL)  
    LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
    STARCH, CORN (UNII: O8232NY3SJ)  
    SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
    D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)  
    Product Characteristics
    ColoryellowScoreno score
    ShapeROUNDSize7mm
    FlavorImprint Code 860;n
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:43386-860-0330 in 1 BOTTLE; Type 0: Not a Combination Product12/04/2015
    2NDC:43386-860-01100 in 1 BOTTLE; Type 0: Not a Combination Product12/04/2015
    3NDC:43386-860-101000 in 1 BOTTLE; Type 0: Not a Combination Product12/04/2015
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA20453412/04/2015
    DEXMETHYLPHENIDATE HYDROCHLORIDE 
    dexmethylphenidate hydrochloride tablet
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:43386-861
    Route of AdministrationORALDEA ScheduleCII    
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    DEXMETHYLPHENIDATE HYDROCHLORIDE (UNII: 1678OK0E08) (DEXMETHYLPHENIDATE - UNII:M32RH9MFGP) DEXMETHYLPHENIDATE HYDROCHLORIDE10 mg
    Inactive Ingredients
    Ingredient NameStrength
    ANHYDROUS CITRIC ACID (UNII: XF417D3PSL)  
    LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
    STARCH, CORN (UNII: O8232NY3SJ)  
    SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
    Product Characteristics
    ColorwhiteScoreno score
    ShapeROUNDSize7mm
    FlavorImprint Code 861;n
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:43386-861-0330 in 1 BOTTLE; Type 0: Not a Combination Product12/04/2015
    2NDC:43386-861-01100 in 1 BOTTLE; Type 0: Not a Combination Product12/04/2015
    3NDC:43386-861-101000 in 1 BOTTLE; Type 0: Not a Combination Product12/04/2015
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA20453412/04/2015
    Labeler - Lupin Pharmaceuticals,Inc. (089153071)
    Registrant - Novel Laboratories, Inc. (793518643)
    Establishment
    NameAddressID/FEIBusiness Operations
    Novel Laboratories, Inc.793518643analysis(43386-860, 43386-861, 43386-862) , manufacture(43386-860, 43386-861, 43386-862) , pack(43386-860, 43386-861, 43386-862)